The overall aims of the research project are to gain an understanding of how DNA binding ligands discriminate between different base pair sequences, and to examine the influence of base pair sequence on conformational properties of DNA. Laser Raman spectroscopy is used to determine conformational features of the binding of netropsin and distamycin to DNA. These drugs show high specificity for AT base paired regions of DNA. Calculation of low energy conformations of these drugs complexed to DNA will be carried out. Initial conditions and parameters of the complexes are based on experimental data. Raman spectroscopy will be used to examine conformational features of natural DNAs and synthetic DNA polymers and oligomers. Studies are planned to monitor the B yields A conformation induced by increasing ethanol concentration. Raman spectra studies of block DNAs of the type d (C10A5) d (T5G10) are planned. Analysis of this DNA and the DNAs poly d(A) poly d(T) and poly D(G) poly d(C) should provide information about the conformation of these block sequences when adjacent to similar and different sequences.